How do Shp2 mutations that oppositely influence its biochemical activity result in syndromes with overlapping symptoms?

Activating and inactivating mutations of SHP-2 are responsible, respectively, for the Noonan (NS) and the LEOPARD (LS) syndromes. Clinically, these developmental disorders overlap greatly, resulting in the apparent paradox of similar diseases caused by mutations that oppositely influence SHP-2 phosphatase activity. While the mechanisms remain unclear, recent functional analysis of SHP-2, along with the identification of other genes involved in NS and in other related syndromes (neurofibromatosis-1, Costello and cardio-facio-cutaneous syndromes), strongly suggest that Ras/MAPK represents the major signaling pathway deregulated by SHP-2 mutants. We discuss the idea that, with the exception of LS mutations that have been shown to exert a dominant negative effect, all disease-causing mutations involved in Ras/MAPK-mediated signaling, including SHP-2, might lead to enhanced MAPK activation. This suggests that a narrow range of MAPK signaling is required for appropriate development. We also discuss the possibility that LS mutations may not simply exhibit dominant negative activity. Received 30 November 2006; received after revision 8 February 2007; accepted 13 March 2007     

固化盐渍土的自生体积稳定性

为避免盐渍土在固化过程中可能发生的体积变形危害,研究其自生体积稳定性。制备了290mm长的试件,利用高精度位移测量系统,测试了不同含量的氯盐与硫酸盐在不同固化剂体系下引起的固化土的线性膨胀/收缩率,分析了C a2 、N a 以及含水率对膨胀/收缩率的影响。结果表明:固化氯盐盐渍土不会发生较大的体积变形,而固化硫酸盐盐渍土可能引起巨大的膨胀率;采用矿渣-粉煤灰-水泥复合固化剂,参与化学反应而产生膨胀性产物的C a2 减少,可以降低固化盐渍土的膨胀率。当C a2 不足而N a 充分时,氯盐和硫酸盐不会对化学反应起促进作用。含水率会影响固化土结构的疏密程度以及膨胀性产物的生长位置。     

Molecular cloning and expression of interleukin Ibeta (IL-1β) from red seabream (Pagrus major)

The interleukin 1β (IL-1β) cDNA was cloned from the red seabream (Pagrus major) by homology cloning strategy. A cDNA fragment was amplified by PCR using two degenerated primers, which were designed according to the conserved regions of other known IL-1β sequences, and elongated by 3' ends and 5' ends RACE PCR to get the full length coding sequence of red seabream IL-1β (RS IL-1β). The sequence contained 1252 nucleotides that included a 5' untranslated region (UTR) of 84bp, a 3' UTR of 410 bp and an open reading frame (ORF) of 759 nucleotides which could be translated into a putative peptide of 253 amino acids with molecular weight of 28.6 kD and putative isoelectric point pI of 5.29. The deduced peptide contained two potential N-glycosylation sites and an identifiable IL1 family signature, but lacked the signal peptide and the clear ICE cut site, which were common in other nonmammalian IL-1β genes. The RS IL-1β had the highest homology with piscine IL-1β according to phylogenetic tree analysis.     

Innovation on Petroleum Engineering Technology of China Beach and Shallow Water Areas

1Chinaoffshoreoil&gasresourcesandtheircharacteristicfeatures　Chinaoffshoreoil&gasexplorationstartedduringthe1 95 0s .Until 1 971 ,thecommercialHai 4fieldwasfoundinBohai.Subsequentlytwoproductionplatformswereconstruc ted ,thefirstChinaoffshoreoilfieldwasformed .Fromthenon ,Chinaoffshoreoil&gasexplorationandexploitationspeedbecameprogressivelyfaster.Afteralargeamountofexplorationwork ,theoilandgasresourcesinChinacoastalareasweremadeclearpreliminarily .AccordingtoState sSecondaryResourceEva…     

安全性和正确性折中的软件系统开发方法

主要分析和研究如何在软件当前的现实下寻求功能正确性和安全性的折中策略，来解决商业软件长期以来带有“bug”和安全性问题．对功能正确性和安全性的折中方案，亦有详细的分析，最后还提出将软件开发的折中技术融入软件工程以取得实际的效果．     

过程强化的若干新进展

本文从现代过程工业发展的需求出发，介绍了过程强化的历史和现状，分析了近年来过程强化的特点。本文还结合实例对化工过程强化的作用和存在的问题等进行了讨论。     

开关型磁阻电动机的振动分析

针对SR电动机存在的振动和噪声问题,分别应用实验模态分析法和计算模态分析法研究了SR电动机的动力特性,得到了SR电动机定子的固有频率和主振型,计算值与实验测量值吻合较好,所得数据可为制定抑制SR电动机的振动和噪声方案提供参考.     

凝聚环的几个特征

证明了对于一个环R，下列条件等价：(1)R是左凝聚的；(2)对任意正整数n，Mn(R)是左1-凝聚的；(3)Ext^2R(R／I，N)=0对于任意有限生成左理想I及F-内射模RN成立；(4)若N1≤N都是F-内射左R-模，则N／N1也是F-内射模．     

玉米两个自交系及其杂交F_1染色体G-带带型的比较

对玉米两个自交系京7和华5及其杂交F_1的染色体G-带带型进行了比较研究。结果表明,两自交系的G-带中A型带之间的相似点很多,有的完全一致;而B型带在带的数目和分布位置上有差异。杂交F_1的G-带带型具有杂合性,B型带的杂合性尤为明显。文中讨论了G-带、C-带和N-带并存等问题。     

一类新型双杂环衍生物的合成及其杀菌活性

三唑并嘧啶类杂环衍生物由于其分子结构中同时包含了三唑及嘧啶这两类重要的活性结构单元 ,因而往往表现出广泛的生物活性[1～ 4] ,既可以用于医药 ,也可以用于农药 .因此 ,近年来关于三唑并嘧啶类衍生物的合成及其生物活性的研究受到了人们的广泛关注 -二甲基 - 1 ,2 ,4-三唑